4. Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine.
Institute of Applied Complementary Medicine Inc. 1997.
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1. Murry M. The Healing Power of Herbs. Prima Publishing 1995:286-93
2. Muntzing J et al. Direct and indirect effect of docosanol, the active principle in Tadenan, on the rat prostate. Invest Urol 1979;17:176-80
3. Thieblot L. Preventive and curative action of Pygeum africanum extracts on experimental prostatic adenoma in the rat. Therapie
1975;26:575-80
4. Hinman F. Benign Prostatic Hyperplasia. Springer-Verlag, NY 1983
5. Bombardelli E. Methods, composition and compounds for the tratment of prostatic adenoma. European Patent Appl 8330491.3, June 10,
1985
6. Marcoli M. Anti-inflammatory and antiedemigenic activity of extract of Pygeum africanum in the rat. New Trends Androl Sci 1985;1:89
7. Guillemin P. Clinical trials of V1326, or Tadenan, in prostatic adenoma. Med Pract 1970;386:75-6
8. Lange J, Muret P. Clinical trial of V1326 in prostatic disease. Medicine 1970;11:2807-11
9. Wemeau L, Delmay J, Blankaert J. Tadenan in prostatic adenoma. Vie Medicale January 1980:585-8
10. Viollet G. Clinical experimentation of a new drug from prostatic adenoma. Vie Medicale June, 1970:3457-8
11. Lhez A, Leguevague G. Clinical trials of a new lipid-sterolic complex of vegetal origin in the tratment of prostatic adenoma. Vie Medicale
December 1970:5399-5404
12. Thomas JP, Rouffilange F. The action of Tadenan in prostatic adenoma. Rev Int Serv 1970;43:43-5
13. Huet, JA. Prostatic disease in old age. Med Intern 1970;5:405-8
14. Rometti A. Medical treatment of prostatic adenoma. La provence medicale 1970;38:49-51
15. Gallizia F, Gallizia G. Medical treatment of benign prostatic hypertrophy with a new phytotherapeutic principle. Recent Med 1972;9:461-8
16. Durval A. The use of a new drug in the treatment of prostatic disorders. Minerva Urol 1970;22:106-11
17. \Pansadoro V, Benincasa A. Prostatic hypertrophy:Results obtained with Pygeum africanum extract. Minerva Med 1972;11:119-44
18. Zurita EI, Pecorini M, Cuzzoni G. Treatment of prostatic hypertrophy with Pygeum africanum extract. Rev Bras Med 1984;41:364-6
19. Maver A. Medical therapy of the fibrous-adematose hypertrophy of the prostate with a new vegetal substance. Minerva Med
1972;63:2126-36
20. Bongi G. Tadenan in the treatment of prostatic adenoma. Minerva urol 1972;24:129-39
21. Doremieux J, Masson JC, Bollack C. Prostatic hypertrophy, clinical effects and histological changes produced by a lipid complex
extracted from Pygeum africanum. J med Strasbourg 1973;4:253-257
22. Del Valio B. The use of a new drug in the treatment of chornic prostatitis. Minerva Urol 1974;26:81-94
23. Colpi G, Farina U. Study of the activity of chloroformic extract of Pygeum africanum bark in the treatment of urethral obstructive syndrome
caused by non-cancerous prostapathy. Urologia 1976;43:441-8
24. Donkervoort T et al. A clinical and urodynamic study of Tadenan in the treatment of benign prostatic hypertrophy. Urology 1977;8:218-25
25. Dufour B, Choquenet C. Trial controlling the effects of Pygeum africanum extract on the functional symptoms of prostatic adenoma. Ann
Urol 1984;18:193-5
26. Legramandi C, Ricci-Barbini V, Fonte A. The importance of Pygeum africanum in the treatment of chronic prostatitis void of bacteria. Gaz
Medica Ital 1984;143:73-6
27. Ranno S et al. Efficacy and tolerability in the treatment of prostatic adenoma with Tadenan 50. Progresso Medico 1986;42:165-9
28. Frasseto G et al. Study of the efficacy and tolerability of Tadenan 50 in patients with prostatic hypertrophy. Progresso Medico 1986;42:49-
52
29. Bassi P et al. Standardized extract of Pygeum africanum in the treatment of benign prostatic hypertrophy. Minerva Urol 1987;39:45-50
30. Barlet A et al. Efficacy of Pygeum africanum extract in the medical therapy of urination disorders due to benign prostatic hyperplasia:
Evaluation of objective and subjective parameters. A placebo-controlled double-blind multicenter study. Wien Klin Wochenschr
1990;102:667-73
31. Healthnotes Online. Healthnotes Inc, 2000;www.healthnotes.com:Pygeum
32. Natural Product Encyclopedia. www.consumerslab.com:Pygeum
33. Andro MC, Riffaud JP. Pygeum africanum extrct for the treatment of patients with benign prostatic hyperplasia:a review of 25 years of
published experience. Vurr Ther Res 1995;56:796-817
34. Yablonsky F, Nicolas V, Riffaud JP et al. Antiproliferative effect of Pygeum africanum extract on rat prostatic fibroblasts. J Urol
1997;157:2381-7
35. Bombardelli E, Morazzoni P. Prunus africana (Hook, f.)Kalkm. Fitoterapia. 1997;68:205-18
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Red Clover (Trifolium pratense)
General Features
Interest in the physiological effects of phytoestrogens (plant-based estrogen) found in many plants first arose in
Australia, during the 1940’s, when it was observed that sheep grazing on various species of clover became infertile. It
was several decades later, when results from epidemiological studies suggested that the dietary consumption of soy
products might have a protective role in breast cancer. Subsequent research indicates that much of this protective
effect appears to be related to the presence of isoflavones, which also possess phytoestrogen activity. Studies have
shown that supplementation with soy isoflavones can help reduce hot flashes and related menopausal symptoms,
favorably modulate hormonal levels in premenopausal women, increase levels of sex hormone-binding globulin
(SHBG), which is deemed to be a favorable effect for protection against reproductive cancers, and help reduce risk of
coronary heart disease in women. Soy isoflavones have also been shown to inhibit the aromatase enzyme in fat
tissue, which converts androstenedione to estrone hormone. Higher levels of estrone hormone are associated with
increased breast cancer risk and thus, isoflavones may provide additional protection from breast cancer by reducing
circulating estrone levels via the inhibition of aromatase enzyme (estrogen synthase). To date a significant number of
studies have evaluated the potential therapeutic and preventive effects of soy isoflavones on reproductive organ
diseases in women and men, bone density and osteoporosis, cardiovascular disease, and the management of
menopausal symptoms, premenstrual syndrome, fibrocystic breast disease, uterine fibroids and endometriosis (see
soy in this document). The positive results from many of these investigations have sparked the interest of researchers,
who are presently exploring the health benefits that may be available from the isoflavones contained within red clover.1
Principle Active Constituents
Red Clover is a rich source of isoflavones and is known to contain all four isoflavones, which include genistein,
diadzein, formononetin, and biochanin A. The predominant isoflavones in soy include genistein and diadzein.
Formononetin can be converted into diadzein, which in turn can be metabolized to equol by bowel bacteria. Equol has
substantially more estrogenic activity than either diadzein or formononetin. Thus, the composition and concentration of
the bacterial flora of the large bowel is an important determinant of how efficiently an individual can synthesize equol
(the most powerful phytoestrogen) and thereby be influenced by its physiological effects. Studies show that there is
great variation in the absorption rate of isoflavones, in general, from one person to the next. Isoflavones occur as
flavone glycosides in soy, Red Clover and other plant foods. As such, the gut bacteria must first split the carbohydrate
molecule away from the isoflavone to convert it to its free, aglycone form (without attachment to a carbohydrate). The
aglycone form is then absorbed into the body and is able to exert its phytoestrogen effects on target tissues. (e.g.,
breast, endometrium, prostate gland, bone etc.). It has been shown that subjects with fewer gut bacteria (possibly
from treatment with antibiotics or other causes) have less ability to absorb phytoestrogens for this reason and that
absorption rates can vary from 13% to 35% depending upon the status of the individual gut microflora. Therefore, in
some cases it may be wise to provide an individual with probiotic and/or prebiotic supplementation in order to restore,
or further support, the gut microflora, and thereby increase the absorption of isoflavones from food and/or
supplements. In general, it has been shown that between 30 to 70% of dietary isoflavones are converted to active
metabolites by gut bacteria and are then able to get absorbed into the bloodstream, and exert their phytoestrogens
effects on target tissues.1,2
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Clinical Application and Mechanism of Action
1. Prevention of Reproductive Organ Diseases In Women
Although no long-term studies in humans exist to prove that Red Clover supplementation can prevent breast cancer
and other female reproductive diseases, high intakes of soy are strongly associated with a significant reduction in
risk. The chemical structure of phytoestrogens is very similar to the body’s own estrogens. Many reproductive
cancers are known to result from, or be promoted by, over-stimulation by the body’s estrogen hormones, as well as
from the use of hormone replacement therapy. Of great importance is the fact that isoflavones, which have only
1/1,000 to 1/10,000 the potency of estradiol (a potent estrogen made by the body), can bind to estrogen receptors
and compete with estrogen in the human body. Isoflavones are a form of “selective estrogen receptor modifier”
(SERM), which preferentially activate the beta estrogen receptors, dominant in the brain, bone and heart, yet show
little affinity for the alpha estrogen receptor in breast and uterine tissue. This is similar to the effect of Tamoxifen,
which is used as a drug to help prevent recurrence of estrogen receptor-positive breast cancer. Over-stimulation of
alpha receptors from estradiol and estrone, tends to result in more rapid cell division and increased risk of breast
cancer. Due to their greater affinity for beta receptors (including breast cells), isoflavones tend to slow the
proliferation rate of breast cells, and breast cancer cells, in the presence of the body’s own estrogens. As such,
isoflavones demonstrate, in experimental and animal models, features suggesting that they have real potential to
prevent breast cancer (and other reproductive cancers), and may also be useful in containing and controlling
existing reproductive cancers in certain cases. Intensive study is underway at this time to determine if this latter
application is valid. Until this is clearly established, women should not take isoflavone supplements of any kind to
help treat existing breast cancer or to help block the recurrence of breast cancer, without the consent of their
attending physician.1,2,3
Although not as potent as estradiol, high intakes of phytoestrogens from food sources and isoflavone-containing
supplements can increase blood levels of phytoestrogens to 1,000 times those of estradiol and other endogenous
(made by the body) estrogens. Phytoestrogens compete with the body’s own estrogen for receptor sites (on the
breast, bone, prostate, brain, cervix, etc.) and if endogenous levels are high, isoflavones have been shown to exhibit
anti-estrogenic properties, toning down the dangerous over-stimulation effect of the body’s own estrogens. If
endogenous estrogen levels are low (as occurs in menopause), isoflavones can produce estrogenic effects to help
manage menopausal symptoms.7
2. Menopausal Symptoms
A preliminary study involving 23 postmenopausal women by Lila Natchtigall (Gynecologist, N.Y.), showed that the
use of 40 mg per day of Red Clover extract reduced the incidence of hot flashes by 50% during the 3-month
period.4 A second open trial revealed that Red Clover extract (40 mg per day) resulted in significant improvement in
night sweats and hot flashes.7 However, a group of researchers from George Washington University and Columbia
University reviewed the scientific evidence for Red Clover in the management of menopause. Publishing their
results in Menopause, the Journal of the North American Menopause Society, they found only two good clinical
trials in which menopausal women were randomly given Red Clover extracts or a placebo for three months.
Neither of the trials found Red Clover to be better than placebo for hot flashes or vaginal dryness, and found no
benefit on blood cholesterol. As of December 2001, the Harvard Women’s Health Watch suggests that women
would be better off spending their money on supplements that contain soy, not red clover, as soy has been shown
to consistently improve menopausal symptoms and reduce high cholesterol levels in postmenopausal women, to a
modest, but significant degree.4,5,6,7
By contrast, the use of hormone replacement therapy (HRT) has been shown to be very effective in managing
menopausal symptoms, but is associated with a significant increase in risk of breast cancer. As a result, only 10-
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35% of postmenopausal women use it and half of those women discontinue HRT within a year, often due to side
effects such as bleeding and breast pain or because of concerns about breast or uterine cancer, and
thromboembolic disease. In fact, HRT is contraindicated in about 10% of postmenopausal women, including those
who have a history of estrogen-dependent malignancy (breast cancer, uterine cancer, etc.), clotting disorders
associated with estrogen use or active liver or thromboembolic disease.
It is interesting to note that 85% of North American women experience hot flashes and other vasomotor changes
during menopause, whereas a study of menopausal Thai women revealed that only 27% of these women experience
these menopausal symptoms. A study of Japanese women noted a similar finding. Researchers believe that the
higher intake of isoflavones in the traditional Asian diet accounts for the lower incidence of menopausal symptoms
experienced by Asian women. This is further supported by migration studies that indicate that Asian women living in
North America who abandon their traditional dietary patterns have a higher incidence of chronic and degenerative
diseases, including hormone-dependent cancers, colon cancer, and cardiovascular disease compared with those who
consume traditional Japanese diets. Other studies have shown that postmenopausal women with higher urinary
excretion of isoflavones (a marker for higher intake and higher blood levels of isoflavones) demonstrate a significant
reduction in hot flashes compared to women who excrete less than 2 mg of urinary isoflavones per day, on average (in
women not using HRT).7
Author’s Note: At this time, it appears that soy isoflavones and black cohosh provide the most reliable relief of
menopausal symptoms and are also the safest natural interventions to use, regarding contraindications, side effects
and drug-nutrient interactions. (See Soy and Black Cohosh in this document)
3. Bone Density and Osteoporosis
Red Clover has been evaluated for its potential ability to support bone density through the effects of its phytoestrogen
content. A one year trial (double-blind, placebo-controlled) involving 107 women showed that 40 mg of Red Clover
extract decreased the rate of bone mineral density loss and bone mineral content reduction in the lumbar spine in pre
and peri-menopausal women. No effect was seen in the hip or in urinary bone markers. Another study found that Red
Clover extract supplementation increased bone mineral density in the proximal radius and ulna. 7,8 Studies using soy
have also demonstrated a positive effect on bone density as well as the use of ipriflavone, a derivative of soy
isoflavones.7
4. Cholesterol Lowering
A review of the scientific literature revealed that three out of four clinical trials involving postmenopausal women found
that Red Clover did not reduce high cholesterol or produce any significant changes to serum lipid levels.6,9 By
comparison, evidence supports the use of soy extract and soy foods as a natural cholesterol-lowering intervention.7,10
One study did show that Red Clover extract was able to increase HDL-cholesterol by 15 to 29% and reduce serum
apolipoprotein B by 11.5-17% in postmenopausal women, after six months of treatment. These findings require
verification.8
Dosage and Standardized Grade
The most common therapeutic dosage of Red Clover extract yields 40 mg per day of Red Clover
isoflavonoids.2,4,6,7,9
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Adverse Side Effects, Toxicity and Contraindications
Red Clover is considered to be safe when taken in accordance with proper dosing guidelines. However, the
presence of coumarins in Red Clover and Red Clover extract increases the potential for bleeding disorders, and
thus, it should not be combined with anti-coagulant medications. Practitioners and patients should monitor
response to the use of Red Clover for any increased bleeding or bruising tendencies.5,11
Previous history of an estrogen-dependent or reproductive cancer requires that a patient seek clearance from their
attending physician before using a phytoestrogen-containing supplement product, such as red clover.1,2,3
Drug-Nutrient Interactions
Anti-coagulant Medications - The high coumarin content of Red Clover lends itself to an increase risk of bleeding
disorders if combined with aspirin, warfarin, coumadin, heparin, Plavix (clopidogrel), Trental (pentoxifylline), or any
other blood thinner.5,11
Pregnancy and Lactation
During pregnancy and lactation, the only supplements that are considered safe include standard prenatal
vitamin and mineral supplements. All other supplements or dose alterations may pose a threat to the
developing fetus and there is generally insufficient evidence at this time to determine an absolute level of
safety for most dietary supplements other than a prenatal supplement. Any supplementation practices
beyond a prenatal supplement should involve the cooperation of the attending physician (e.g., magnesium
and the treatment of preeclampsia.)
References: Pregnancy and Lactation
1. Encyclopedia of Nutritional Supplements. Murray M. Prima Publishing 1998.
2. Reavley NM. The New Encyclopedia of Vitamins, Minerals, Supplements, and Herbs. Evans and
Company Inc. 1998.
3. The Healing Power of Herbs (2nd edition). Murray M. Prima Publishing 1995.
4. Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine.
Institute of Applied Complementary Medicine Inc. 1997.
1. Mills S and Bone K. Principles and Practice of Phytotherapy. Churchill Livingstone, Publisher:54-6;67-8
2. Medical Post, Oct 3, 2000: Isoflavones and Menopause
3. Dornstauder E, Jisa E, unterrieder I, Krenn L, Kubelka W, Jungbauer A. Estrongenic activity of two standardized red clover
extracts (Menoflavon) intended for large scale use in hormone replacement therapy. J Steroid Biochem Mol Biol 2001 Jul;
78(1):67-75
4. Gower T. New answers to menopause? Health Jan/Feb2002;16(1) p76
5. Robb-Nicholson C. By the way, Doctor: Does red clover work? Harvard Women’s Health Watch Dec2001;9(4):p7
6. Fugh-Berman A, Kronenberg F. Red clover (Trifolium pratense) for menopausal women: current state of knowledge.
Menopause 2001 Sep-Oct;8(5):333-7
7. Nachtigall LE. Isoflavones in the management of menopause. Total Health Jul/Aug2001;23(4):p26
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8. Clifton-Bligh PB, Baber RJ, Fulcher GR, Nery ML, Moreton T. The effect of isoflavones extracted from red clover
(Rimostil) on lipid and bone metabolism. Menopause 2001 Jul-Aug;8(4):259-65
9. Howes JB, Sullivan D, Lai N, Nestel P, Pomeroy S, West L, et al. The effects of dietary supplementation with isoflavones
from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholesterolaemia.
Atherosclerosis 2000 Sep;152(1):143-7
10. Anthony MS, et al. Effects of soy isovlavones on atherosclerosis: potential mechanisms. Am J Clin Nutr Dec1998;68(6
Suppl):1390S-35S
11. Heck AM, DeWitt BA, Lukes Al. Potential interactions between alternative therapies and warfarin. Am J Health Syst Phar
2000 Jul 1;57(13):p1221-7;quiz p1228-30
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Reishi Mushroom Extract
General Features
Reishi Mushroom (Ganoderma lucidum) is called “the mushroom of immortality” in China and has been used in
Oriental Medicine for over 2,000 years.1,2 In recent years its active ingredients have been the subject of intensive
research regarding their apparent ability to help prevent or treat certain types of cancer, aid in the treatment of liver
disease, HIV infection, acute or recurrent herpetic infections, high blood pressure, chronic bronchitis, allergies and
asthma, and favorably modulate immune function.3 The Reishi Mushroom grows wild on decaying logs and tree
stumps in the coastal provinces of China. The fruiting body of the mushroom is used medicinally.4
Principle Active Constituents
1. Specific Polysaccharides: which occur in the form of Beta-D-glucans bound to amino acids. These agents are
shown to possess immune-modulating and anti-cancer properties.3
2. Triterpene compounds known as ganoderic acids: which have been shown to lower blood pressure, reduce platelet
stickiness and may decrease LDL-cholesterol.5
3. Other major active constituents: include sterols, coumarin and mannitol.5
Clinical Application and Mechanism of Action
1. Anti-Cancer Agent
Animal cancer studies have shown a 50% tumor regression outcome with Reishi Mushroom Extract treatment (e.g.,
connective tissue cancer model in mice).6 Reishi Mus